INTERACTION OF SEROTONIN AND NOREPINEPHRINE IN SPINAL ANTINOCICEPTION

The interactions between different doses of serotonin (5-HT) and norep inephrine (NE) in in vivo experiments on rat spinal cord dorsal horn c ells was investigated using the integrated electromyography (EMG) meas urement of the nociceptive hindlimb flexor reflex (FR). The results in dicate that: (1) intrathecal (IT) administration of low doses of 5-HT (60 nmol) or NE (1.5 nmol) suppresses the nociceptive FR by 40% for 20 min, respectively; (2) administration of higher doses of 5-HT (240 nm ol, IT) multiplies the suppression of the nociceptive FR by 80% for 40 min, and NE (15 nmol, IT) produces similar suppression of the nocicep tive FR for 80 min; (3) concomitant administration of low doses of 5-H T (60 nmol, IT) and NE (1.5 nmol, IT) produces a summation of the noci ceptive FR suppression both in amplitude and duration; (4) concomitant administration of the higher doses of 5-HT (240 nmol IT) with NE (15 nmol, IT) produces similar effect obtained as 5-HT given separately, a nd no summation was obtained as observed following the lower dosages; (5) serotonin (240 nmol, IT) given 40 min before NE (15 nmol, IT) atte nuates the duration of the suppression induced by NE; (6) pretreatment with a selective 5-HT2 receptor antagonist ketanserin (60 nmol, IT) f ailed to abolish the 5-HT effects; (7) pretreatment with ketanserin pr ior to concomitant administration of the higher doses of 5-HT and NE p rolongs the time duration of the nociceptive FR suppression. The resul ts suggest that higher dosage of 5-HT attenuates the effects induced b y NE and that 5-HT2 receptor might mediate the attenuation effect of 5 -HT on the NE-induced antinociception at the spinal cord level.